Cyclopropanecarboxylic acid derivative

Abstract

A compound represented by the following general formula (I) or a pharmacologically acceptable salt thereof, wherein R 1 represents a C1 to C6 alkyl group which may be substituted by one to three groups selected from substituent group A, or the like (substituent group A: a hydroxy group, a halogeno group, a cyano group, a nitro group, an amino group, a carboxy group, a C1 to C3 alkyl group, etc.); R 2 , R 3 , and R 8 each independently represent a hydrogen atom or a C1 to C3 alkyl group; R 4 , R 5 , R 6 , R 7 , R 9 , and R 10 each independently represent a hydrogen atom or the like; and R 11 represents a hydrogen atom or the like, has TAFIa enzyme inhibitory activity and is useful as a therapeutic drug for myocardial infarction, angina pectoris, acute coronary syndrome, cerebral infarction, deep vein thrombosis, pulmonary embolism, or the like.

The invention claimed is: 
     
       1. A compound of general formula (I): 
       
         
           
           
               
               
           
         
       
       or a pharmacologically acceptable salt thereof, wherein
 R 1  is selected from a C1 to C6 alkyl group which may be substituted by one to three identical or different groups selected from:
 substituent group A, 
 a C2 to C6 alkenyl group which may be substituted by one to three identical or different groups selected from substituent group A, 
 a C3 to C8 cycloalkyl group which may be substituted by one to three identical or different groups selected from substituent group A, 
 an aryl group which may be substituted by one to three identical or different groups selected from substituent group A, provided that when the aryl group is a phenyl group having a substituent, the substituent is substituted at a meta or para position on the benzene ring, 
 a saturated heterocyclyl group which may be substituted by one to three identical or different groups selected from substituent group A, and 
 an unsaturated heterocyclyl group which may be substituted by one to three identical or different groups selected from substituent group A; 
 
 R 2 , R 3 , and R 8  are each independently selected from a hydrogen atom and a C1 to C3 alkyl group; 
 R 4 , R 5 , R 6 , R 7 , R 9 , and R 10  are each independently selected from a hydrogen atom, a fluoro group, and a C1 to C3 alkyl group; 
 R 11  is selected from a hydrogen atom, a methyl group, and an ethyl group; and 
 substituent group A consists of a hydroxy group, a halogeno group, a cyano group, a nitro group, an amino group, a carboxy group, a C1 to C3 alkyl group, a halogeno-C1 to C3 alkyl group, a C3 to C8 cycloalkyl group, a C1 to C3 alkoxy group, a halogeno-C1 to C3 alkoxy group, a C1 to C3 alkylsulfonyl group, an aryl group, a saturated heterocyclyl group, an unsaturated heterocyclyl group, and an aryloxy group. 
 
     
     
       2. The compound according to  claim 1  or a pharmacologically acceptable salt thereof, wherein R′ is selected from:
 a C1 to C6 alkyl group which may be substituted by one to three identical or different groups selected from a hydroxy group, a halogeno group, an amino group, a C1 to C3 alkyl group, a phenyl group, and a phenoxy group; 
 a C2 to C6 alkenyl group which may be substituted by one to three identical or different groups selected from a hydroxy group, a halogeno group, an amino group, a C1 to C3 alkyl group, a phenyl group, and a phenoxy group; 
 a C3 to C8 cycloalkyl group which may be substituted by one to three identical or different groups selected from a hydroxy group, a halogeno group, an amino group, and a C1 to C3 alkyl group; 
 a phenyl group which may be substituted by one to three identical or different groups selected from a hydroxy group, a halogeno group, a cyano group, an amino group, a C1 to C3 alkyl group, a halogeno-C1 to C3 alkyl group, a C1 to C3 alkoxy group, a C1 to C3 alkylsulfonyl group, and a phenoxy group, provided that when the phenyl group has a substituent, the substituent is substituted at a meta or para position on the benzene ring; 
 a naphthyl group which may be substituted by one to three identical or different groups selected from a hydroxy group, a halogeno group, a cyano group, an amino group, a C1 to C3 alkyl group, a halogeno-C1 to C3 alkyl group, a C1 to C3 alkoxy group, a C1 to C3 alkylsulfonyl group, and a phenoxy group; 
 a pyridyl group which may be substituted by one to three identical or different groups selected from a hydroxy group, a halogeno group, an amino group, a C1 to C3 alkyl group, a halogeno-C1 to C3 alkyl group, a C1 to C3 alkoxy group, a C1 to C3 alkylsulfonyl group, and a phenoxy group; 
 a pyrimidinyl group which may be substituted by one to three identical or different groups selected from a hydroxy group, a halogeno group, an amino group, a C1 to C3 alkyl group, a halogeno-C1 to C3 alkyl group, a C1 to C3 alkoxy group, a C1 to C3 alkylsulfonyl group, and a phenoxy group; and 
 a benzofuranyl group which may be substituted by one to three identical or different groups selected from a hydroxy group, a halogeno group, an amino group, a C1 to C3 alkyl group, a halogeno-C1 to C3 alkyl group, a C1 to C3 alkoxy group, a C1 to C3 alkylsulfonyl group, and a phenoxy group. 
 
     
     
       3. The compound according to  claim 1  or a pharmacologically acceptable salt thereof, wherein R 1  is selected from:
 an unsubstituted C1 to C6 alkyl group; 
 a C2 to C6 alkenyl group which may be substituted by one phenyl group; 
 a C3 to C8 cycloalkyl group which may be substituted by one to three identical or different C1 to C3 alkyl groups; 
 a phenyl group which may be substituted by one to three identical or different groups selected from a halogeno group, a C1 to C3 alkyl group, a halogeno-C1 to C3 alkyl group, a C1 to C3 alkoxy group, a C1 to C3 alkylsulfonyl group, and a phenoxy group, provided that when the phenyl group has a substituent, the substituent is substituted at a meta or para position on the benzene ring; and 
 a pyridyl group which may be substituted by one group selected from a halogeno group, a C1 to C3 alkyl group, and a C1 to C3 alkoxy group; or an unsubstituted pyrimidinyl group. 
 
     
     
       4. The compound according to  claim 1  or a pharmacologically acceptable salt thereof, wherein R 1  is selected from:
 an unsubstituted C1 to C6 alkyl group, 
 a C3 to C8 cycloalkyl group which may be substituted by one C1 to C3 alkyl group, 
 an unsubstituted phenyl group, 
 an unsubstituted pyridyl group, and 
 an unsubstituted pyrimidinyl group. 
 
     
     
       5. The compound according to  claim 1  or a pharmacologically acceptable salt thereof, wherein R 1  is selected from a propyl group, a 3,3-dimethylbutyl group, a 2-phenylvinyl group, a cyclohexyl group, a 4-methylcyclohexyl group, a phenyl group, a 3-fluorophenyl group, a 3-chlorophenyl group, a 3-methylphenyl group, a 4-fluorophenyl group, a 4-chlorophenyl group, a 4-methylphenyl group, a 4-ethylphenyl group, a 4-trifluoromethylphenyl group, a 4-methoxyphenyl group, a 4-phenoxyphenyl group, a 3,4-dimethylphenyl group, a 3,4-difluorophenyl group, a pyridin-2-yl group, a pyridin-3-yl group, a pyridin-4-yl group, a pyrimidin-2-yl group, and a 2-naphthyl group. 
     
     
       6. The compound according to  claim 1  or a pharmacologically acceptable salt thereof, wherein R 1  is selected from a 3,3-dimethylbutyl group, a 4-methylcyclohexyl group, a phenyl group, a pyridin-2-yl group, and a pyrimidin-2-yl group. 
     
     
       7. The compound according to  claim 1  or a pharmacologically acceptable salt thereof, wherein R 2 , R 3 , R 7 , R 8 , R 9 , and R 10  are each a hydrogen atom, and R 4 , R 5 , and R 6  are each independently selected from a hydrogen atom or a C1 to C3 alkyl group. 
     
     
       8. The compound according to  claim 1  or a pharmacologically acceptable salt thereof, wherein R 2 , R 3 , R 6 , R 7 , R 8 , R 9 , and R 10  are each a hydrogen atom, and R 4  and R 5  are each independently selected from a hydrogen atom or a C1 to C3 alkyl group. 
     
     
       9. The compound according to  claim 1  or a pharmacologically acceptable salt thereof, wherein R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , and R 8  are each a hydrogen atom, and R 9  and R 10  are each independently selected from a hydrogen atom or a fluoro group. 
     
     
       10. The compound according to  claim 1  or a pharmacologically acceptable salt thereof, wherein all of R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , and R 10  are hydrogen atoms. 
     
     
       11. The compound according to  claim 1  or a pharmacologically acceptable salt thereof, wherein R 11  is a hydrogen atom. 
     
     
       12. The compound according to  claim 1  or a pharmacologically acceptable salt thereof, wherein the cyclopropane moiety in the general formula (I) has a (1R*,2S*) configuration when all of R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , and R 10  are hydrogen atoms. 
     
     
       13. The compound according to  claim 1  or a pharmacologically acceptable salt thereof, wherein the cyclopropane moiety in the general formula (I) has a (1R,2S) configuration when all of R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , and R 10  are hydrogen atoms. 
     
     
       14. A compound of general formula (Ia): 
       
         
           
           
               
               
           
         
       
       or a pharmacologically acceptable salt thereof, wherein R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , and R 11  are as defined in  claim 1 . 
     
     
       15. A compound of general formula (Ic): 
       
         
           
           
               
               
           
         
       
       or a pharmacologically acceptable salt thereof, wherein R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , and R 11  are as defined in  claim 1 . 
     
     
       16. A compound of general formula (I-1): 
       
         
           
           
               
               
           
         
       
       or a pharmacologically acceptable salt thereof, wherein
 R a  is selected from:
 a C3 to C6 branched alkyl group; 
 a C3 to C6 cycloalkyl group which may be substituted by one or two identical or different C1 to C3 alkyl groups; 
 a phenyl group which may be substituted by one or two identical or different groups selected from the group consisting of a C1 to C3 alkyl group, a C1 to C3 alkoxy group, a phenoxy group, a halogeno group, and a cyano group, wherein the substituent is substituted at the 3- or 4-position, or both, of the phenyl group; 
 a naphthyl group; 
 a 5- or 6-membered heteroaryl group which may be substituted by one or two identical or different groups selected from the group consisting of a C1 to C3 alkyl group, a C1 to C3 alkoxy group, a phenoxy group, a halogeno group, and a cyano group, wherein the heteroaryl group has one or more nitrogen atoms in the ring and may be condensed with a benzene ring; and 
 a benzofuranyl group; and 
 
 R b  and R e  are each independently selected from a hydrogen atom or a C1 to C3 alkyl group. 
 
     
     
       17. The compound according to  claim 16  or a pharmacologically acceptable salt thereof, wherein
 R a  is selected from:
 a C4 to C6 branched alkyl group; 
 a C5 to C6 cycloalkyl group which may be substituted by a C1 to C3 alkyl group; 
 a phenyl group which may be substituted by one or two identical or different groups selected from the group consisting of a C1 to C3 alkyl group, a C1 to C3 alkoxy group, a phenoxy group, a halogeno group, and a cyano group, wherein the substituent is substituted at the 3- or 4-position, or both, of the phenyl group; 
 a naphthyl group; 
 a pyridin-2-yl group which may be substituted by a C1 to C3 alkyl group, a C1 to C3 alkoxy group, or a halogeno group, wherein the substituent is substituted at the 4- or 5-position of the pyridyl group; 
 a pyrimidin-2-yl group; 
 a thiazol-2-yl group; 
 a quinolyl group; 
 an isoquinolyl group; and 
 a benzofuranyl group; and 
 
 R b  and R c  are each independently selected from a hydrogen atom and a C1 to C3 alkyl group. 
 
     
     
       18. The compound according to  claim 16  or a pharmacologically acceptable salt thereof, wherein
 R a  is selected from:
 a C5 to C6 branched alkyl group; 
 a cyclohexyl group which may be substituted by a methyl group or an ethyl group; 
 a phenyl group which may be substituted by one or two identical or different groups selected from the group consisting of a methyl group, an ethyl group, a methoxy group, a phenoxy group, a fluoro group, a chloro group, and a cyano group, wherein the substituent is substituted at the 3- or 4-position, or both, of the phenyl group; 
 a 2-naphthyl group; 
 a pyridin-2-yl group which may be substituted by a methyl group, an ethyl group, a methoxy group, a fluoro group, or a chloro group, wherein the substituent is substituted at the 4- or 5-position of the pyridyl group; 
 a pyrimidin-2-yl group; 
 a quinolin-2-yl group; 
 an isoquinolin-3-yl group; and 
 a benzofuran-5-yl group; and 
 
 R b  and R c  are each independently selected from a hydrogen atom, a methyl group, and an ethyl group. 
 
     
     
       19. The compound according to  claim 16  or a pharmacologically acceptable salt thereof, wherein
 R a  is selected from:
 a C6 branched alkyl group; 
 a cyclohexyl group which may be substituted by a methyl group; 
 a phenyl group which may be substituted by a methyl group, a fluoro group, a chloro group, or a cyano group, wherein the substituent is substituted at the 4-position of the phenyl group; 
 a 2-naphthyl group; 
 a pyridin-2-yl group which may be substituted by a methyl group, a methoxy group, or a fluoro group, wherein the substituent is substituted at the 4- or 5-position of the pyridyl group; 
 a pyrimidin-2-yl group; 
 an isoquinolin-3-yl group; and 
 a benzofuran-5-yl group; 
 
 R b  is selected from a hydrogen atom and a methyl group; and 
 R c  is selected from a hydrogen atom, a methyl group, and an ethyl group. 
 
     
     
       20. The compound according to  claim 16  or a pharmacologically acceptable salt thereof, wherein
 R a  is selected from a 3,3-dimethylbutyl group, a cyclohexyl group, a 4-methylcyclohexyl group, a phenyl group, a 4-methylphenyl group, a 4-fluorophenyl group, a 4-chiorophenyl group, a 4-cyanophenyl group, a 2-naphthyl group, a pyridin-2-yl group, a 4-methylpyridin-2-yl group, a 5-methylpyridin-2-yl group, a 4-methoxypyridin-2-yl group, a 4-fluoropyridin-2-yl group, a pyrimidin-2-yl group, an isoquinolin-3-yl group, and a benzofuran-5-yl group; 
 R b  is selected from a hydrogen atom and a methyl group; and 
 R c  is selected from a hydrogen atom, a methyl group, and an ethyl group. 
 
     
     
       21. A compound of general formula (I-2): 
       
         
           
           
               
               
           
         
       
       or a pharmacologically acceptable salt thereof, wherein
 R a  is selected from:
 a C3 to C6 branched alkyl group; 
 a C3 to C6 cycloalkyl group which may be substituted by one or two identical or different C1 to C3 alkyl groups; 
 a phenyl group which may be substituted by one or two identical or different groups selected from the group consisting of a C1 to C3 alkyl group, a C1 to C3 alkoxy group, a phenoxy group, a halogeno group, and a cyano group, wherein the substituent is substituted at the 3- or 4-position, or both, of the phenyl group; 
 a naphthyl group; 
 a 5- or 6-membered heteroaryl group which may be substituted by one or two identical or different groups selected from the group consisting of a C1 to C3 alkyl group, a C1 to C3 alkoxy group, a phenoxy group, a halogeno group, and a cyano group, wherein the heteroaryl group has one or more nitrogen atoms in the ring and may be condensed with a benzene ring; and 
 a benzofuranyl group; and 
 
 R b  and R c  are each independently selected from a hydrogen atom and a C1 to C3 alkyl group. 
 
     
     
       22. The compound according to  claim 21  or a pharmacologically acceptable salt thereof, wherein
 R a  is selected from:
 a C4 to C6 branched alkyl group; 
 a C5 to C6 cycloalkyl group which may be substituted by a C1 to C3 alkyl group; 
 a phenyl group which may be substituted by one or two identical or different groups selected from the group consisting of a C1 to C3 alkyl group, a C1 to C3 alkoxy group, a phenoxy group, a halogeno group, and a cyano group, wherein the substituent is substituted at the 3- or 4-position, or both, of the phenyl group; 
 a naphthyl group; 
 a pyridin-2-yl group which may be substituted by a C1 to C3 alkyl group, a C1 to C3 alkoxy group, or a halogeno group, wherein the substituent is substituted at the 4- or 5-position of the pyridyl group; 
 a pyrimidin-2-yl group; 
 a thiazol-2-yl group; 
 a quinolyl group; 
 an isoquinolyl group; and 
 a benzofuranyl group; and 
 
 R b  and R c  are each independently selected from a hydrogen atom or a C1 to C3 alkyl group. 
 
     
     
       23. The compound according to  claim 21  or a pharmacologically acceptable salt thereof, wherein
 R a  is selected from:
 a C5 to C6 branched alkyl group; 
 a cyclohexyl group which may be substituted by a methyl group or an ethyl group; 
 a phenyl group which may be substituted by one or two identical or different groups selected from the group consisting of a methyl group, an ethyl group, a methoxy group, a phenoxy group, a fluoro group, a chloro group, and a cyano group, wherein the substituent is substituted at the 3- or 4-position, or both, of the phenyl group; 
 a 2-naphthyl group; 
 a pyridin-2-yl group which may be substituted by a methyl group, an ethyl group, a methoxy group, a fluoro group, or a chloro group, wherein the substituent is substituted at the 4- or 5-position of the pyridyl group; 
 a pyrimidin-2-yl group; 
 a quinolin-2-yl group; 
 an isoquinolin-3-yl group; and 
 a benzofuran-5-yl group; and 
 
 R b  and R c  are each independently selected from a hydrogen atom, a methyl group, and an ethyl group. 
 
     
     
       24. The compound according to  claim 21  or a pharmacologically acceptable salt thereof, wherein R a  is selected from:
 a C6 branched alkyl group; 
 a cyclohexyl group which may be substituted by a methyl group; 
 a phenyl group which may be substituted by a methyl group, a fluoro group, a chloro group, or a cyano group, wherein the substituent is substituted at the 4-position of the phenyl group; 
 a 2-naphthyl group; 
 a pyridin-2-yl group which may be substituted by a methyl group, a methoxy group, or a fluoro group, wherein the substituent is substituted at the 4- or 5-position of the pyridyl group; 
 a pyrimidin-2-yl group; 
 an isoquinolin-3-yl group; and 
 a benzofuran-5-yl group; 
 R b  is selected from a hydrogen atom and a methyl group; and 
 R c  is selected from a hydrogen atom, a methyl group, and an ethyl group. 
 
     
     
       25. The compound according to  claim 21  or a pharmacologically acceptable salt thereof, wherein
 R a  is selected from a 3,3-dimethylbutyl group, a cyclohexyl group, a 4-methylcyclohexyl group, a phenyl group, a 4-methylphenyl group, a 4-fluorophenyl group, a 4-chlorophenyl group, a 4-cyanophenyl group, a 2-naphthyl group, a pyridin-2-yl group, a 4-methylpyridin-2-yl group, a 5-methylpyridin-2-yl group, a 4-methoxypyridin-2-yl group, a 4-fluoropyridin-2-yl group, a pyrimidin-2-yl group, an isoquinolin-3-yl group, and a benzofuran-5-yl group; 
 R b  is selected from a hydrogen atom and a methyl group; and 
 R c  is selected from a hydrogen atom, a methyl group, and an ethyl group. 
 
     
     
       26. The compound according to  claim 1  or a pharmacologically acceptable salt thereof, wherein the compound is selected from the group consisting of
 2-(3-aminopropyl)-1-[1-(3,3-dimethylbutyl)-1H-imidazol-4-yl]cyclopropanecarboxylic acid, 
 2-(3-aminopropyl)-1-(1-propyl-1H-imidazol-4-yl)cyclopropanecarboxylic acid, 
 2-(3-aminopropyl)-1-(1-cyclohexyl-1H-imidazol-4-yl)cyclopropanecarboxylic acid, 
 2-(3-aminopropyl)-1-[1-(trans-4-methylcyclohexyl)-1H-imidazol-4-yl]cyclopropanecarboxylic acid, 
 2-(3-aminopropyl)-1-(1-phenyl-1H-imidazol-4-yl)cyclopropanecarboxylic acid, 
 2-(3-aminopropyl)-1-[1-(4-methylphenyl)-1H-imidazol-4-yl]cyclopropanecarboxylic acid, 
 2-(3-aminopropyl)-1-[1-(3-methylphenyl)-1H-imidazol-4-yl]cyclopropanecarboxylic acid, 
 2-(3-aminopropyl)-1-[1-(3,4-dimethylphenyl)-1H-imidazol-4-yl]cyclopropanecarboxylic acid, 
 2-(3-aminopropyl)-1-[1-(4-ethylphenyl)-1H-imidazol-4-yl]cyclopropanecarboxylic acid, 
 2-(3-aminopropyl)-1-[1-(4-methoxyphenyl)-1H-imidazol-4-yl]cyclopropanecarboxylic acid, 
 2-(3-aminopropyl)-1-{1-[4-(trifluoromethyl)phenyl]-1H-imidazol-4-yl}cyclopropanecarboxylic acid, 
 2-(3-aminopropyl)-1-{1-[(E)-2-phenylvinyl]-1H-imidazol-4-yl}cyclopropanecarboxylic acid, 
 2-(3-aminopropyl)-1-[1-(4-fluorophenyl)-1H-imidazol-4-yl]cyclopropanecarboxylic acid, 
 2-(3-aminopropyl)-1-[1-(4-phenoxyphenyl)-1H-imidazol-4-yl]cyclopropanecarboxylic acid, 
 2-(3-aminopropyl)-1-[1-(3,4-difluorophenyl)-1H-imidazol-4-yl]cyclopropanecarboxylic acid, 
 2-(3-aminopropyl)-1-[1-(4-chlorophenyl)-1H-imidazol-4-yl]cyclopropanecarboxylic acid, 
 2-(3-aminopropyl)-1-[1-(3-chlorophenyl)-1H-imidazol-4-yl]cyclopropanecarboxylic acid, 
 2-(3-aminopropyl)-1-[1-(2-naphthyl)-1H-imidazol-4-yl]cyclopropanecarboxylic acid, 
 2-(3-aminopropyl)-1-[1-(3-fluorophenyl)-1H-imidazol-4-yl]cyclopropanecarboxylic acid, 
 2-(3-aminopropyl)-1-(1-pyridin-4-yl-1H-imidazol-4-yl)cyclopropanecarboxylic acid, 
 2-(3-aminopropyl)-1-(1-pyridin-3-yl-1H-imidazol-4-yl)cyclopropanecarboxylic acid, 
 2-(3-aminopropyl)-1-(1-pyridin-2-yl-1H-imidazol-4-yl)cyclopropanecarboxylic acid, 
 ethyl 2-(3-aminopropyl)-1-[1-(4-methylphenyl)-1H-imidazol-4-yl]cyclopropanecarboxylate, 
 2-(3-amino-2-methylpropyl)-1-(1-phenyl-1H-imidazol-4-yl)cyclopropanecarboxylic acid, 
 2-(3-amino-1-methylpropyl)-1-(1-phenyl-1H-imidazol-4-yl)cyclopropanecarboxylic acid, 
 2-(3-aminopropyl)-1-[1-(2-thienyl)-1H-imidazol-4-yl]cyclopropanecarboxylic acid, 
 2-(3-aminopropyl)-1-[1-(5-methylpyridin-2-yl)-1H-imidazol-4-yl]cyclopropanecarboxylic acid, 
 2-(3-aminopropyl)-1-[1-(1,3-thiazol-2-yl)-1H-imidazol-4-yl]cyclopropanecarboxylic acid, 
 2-(3-aminopropyl)-1-(1-pyrimidin-2-yl-1H-imidazol-4-yl)cyclopropanecarboxylic acid, 
 2-(3-aminopropyl)-1-[1-(4-cyanophenyl)-1H-imidazol-4-yl]cyclopropanecarboxylic acid, 
 2-(3-amino-2,2-dimethylpropyl)-1-(1-phenyl-1H-imidazol-4-yl)cyclopropanecarboxylic acid, 
 2-(3-aminopropyl)-1-[1-(5-fluoropyridin-2-yl)-1H-imidazol-4-yl]cyclopropanecarboxylic acid, 
 2-(3-aminopropyl)-1-(1-quinolin-2-yl-1H-imidazol-4-yl)cyclopropanecarboxylic acid, 
 2-[(2-aminomethyl)butyl]-1-(1-phenyl-1H-imidazol-4-yl)cyclopropanecarboxylic acid, 
 2-(3-aminopropyl)-1-[ 1-(1-benzofuran-5-yl)-1H-imidazol-4-yl]cyclopropanecarboxylic acid, 
 2-(3-aminopropyl)-1-[1-(5-methoxypyridin-2-yl)-1H-imidazol-4-yl]cyclopropanecarboxylic acid, 
 2-(3-aminopropyl)-1-[1-(1-naphthyl)-1H-imidazol-4-yl]cyclopropanecarboxylic acid, 
 2-(3-amino-2-methylpropyl)-1-(1-pyridin-2-yl-1H-imidazol-4-yl)cyclopropanecarboxylic acid, 
 2-(3-amino-2-methylpropyl)-1-[1-(5-methylpyridin-2-yl)-1H-imidazol-4-yl]cyclopropanecarboxylic acid, and 
 2-[2-(aminomethyl)butyl]-1-(1-pyridin-2-yl-1H-imidazol-4-yl)cyclopropanecarboxylic acid. 
 
     
     
       27. The compound according to  claim 1  or a pharmacologically acceptable salt thereof, wherein the compound is selected from the group consisting of
 2-(3-aminopropyl)-1-(1-phenyl-1H-imidazol-4-yl)cyclopropanecarboxylic acid, 
 2-(3-aminopropyl)-1-[1-(3,3-dimethylbutyl)-1H-imidazol-4-yl]cyclopropanecarboxylic acid, 
 2-(3-aminopropyl)-1-[1-(trans-4-methylcyclohexyl)-1H-imidazol-4-yl]cyclopropanecarboxylic acid, 
 2-(3-aminopropyl)-1-(1-pyridin-2-yl-1H-imidazol-4-yl)cyclopropanecarboxylic acid, 
 2-(3-amino-2-methylpropyl)-1-(1-phenyl-1H-imidazol-4-yl)cyclopropanecarboxylic acid, 
 2-(3-aminopropyl)-1-[1-(5-methylpyridin-2-yl)-1H-imidazol-4-yl]cyclopropanecarboxylic acid, 
 2-[(2-aminomethyl)butyl]-1-(1-phenyl-1H-imidazol-4-yl)cyclopropanecarboxylic acid, 
 2-[(2R)-3-amino-2-methylpropyl]-1-(1-pyridin-2-yl-1H-imidazol-4-yl)cyclopropanecarboxylic acid, 
 2-[(2R)-3-amino-2-methylpropyl]-1-[1-(5-methylpyridin-2-yl)-1H-imidazol-4-yl]cyclopropanecarboxylic acid, and 
 2-[(2R)-2-(aminomethyl)butyl]-1-(1-pyridin-2-yl-1H-imidazol-4-yl)cyclopropanecarboxylic acid. 
 
     
     
       28. The compound according to  claim 1  or a pharmacologically acceptable salt thereof, wherein the compound is selected from the group consisting of
 (1R,2S)-2-(3-aminopropyl)-1-(1-phenyl-1H-imidazol-4-yl)cyclopropanecarboxylic acid, 
 (1R,2S)-2-(3-aminopropyl)-1-(1-pyridin-2-yl-1H-imidazol-4-yl)cyclopropanecarboxylic acid, 
 (1R,2S)-2-[(2R)-3-amino-2-methylpropyl]-1-(1-pyridin-2-yl-1H-imidazol-4-yl)cyclopropanecarboxylic acid, 
 (1R,2S)-2-[(2R)-3-amino-2-methylpropyl]-1-[1-(5-methylpyridin-2-yl)-1H-imidazol-4-yl]cyclopropanecarboxylic acid, and 
 (1R,2S)-2-[(2R)-2-(aminomethyl)butyl]-1-(1-pyridin-2-yl-1H-imidazol-4-yl)cyclopropanecarboxylic acid. 
 
     
     
       29. A TAFIa inhibitor comprising a compound according to  claim 1  or a pharmacologically acceptable salt thereof. 
     
     
       30. A fibrinolysis promoter comprising a compound according to  claim 1  or a pharmacologically acceptable salt thereof. 
     
     
       31. A pharmaceutical composition containing a compound according to  claim 1  or a pharmacologically acceptable salt thereof and a pharmacologically acceptable carrier.